St. John’s wort may ease mild depression, but it can undercut your other medicines

Key takeaways

• A 2008 Cochrane review of 29 trials with 5,489 people found St. John’s wort extracts beat placebo and matched standard antidepressants, though smaller trials and those from German-speaking countries looked rosier⁷.
• In 2000, two weeks of the herb cut blood levels of an HIV drug by more than half in healthy volunteers², and doctors in Zurich linked it to two heart transplant rejections³.
• The herb’s effect on drug-clearing enzymes wears off within about a week of stopping, so levels of some drugs can climb, and changes in either direction need your prescriber’s help⁶¹¹.
• Ireland ended over-the-counter sales in 2000⁴⁵, and Europe’s official herbal monograph backs only specific extracts, at set doses, for depression⁶.
• If you or someone you know is thinking about suicide, call or text 988¹², and talk with your provider before stopping an antidepressant¹³.

In February 2000, one herb set off alarms on two continents in less than three weeks.

On February 10, the U.S. Food and Drug Administration (FDA) issued a public health advisory about St. John’s wort and HIV drugs¹.

Two days later, The Lancet published two short reports²³. In one, federal researchers found that two weeks of the herb slashed blood levels of the HIV drug indinavir².

In the other, doctors at University Hospital Zurich described two heart transplant patients whose bodies began rejecting their new hearts. They traced it to the herb’s effect on cyclosporine, the drug that prevents rejection³.

By February 29, Britain’s drug safety committee had warned against combining the herb with 10 widely used drugs or drug classes¹. That same year, Ireland ended over-the-counter sales⁴⁵.

None of this means St. John’s wort doesn’t work for mood. European regulators accept certain extracts for mild to moderate depression, and dozens of trials have tested it⁶⁷.

That’s the point. St. John’s wort acts like a drug, so it deserves the care a drug gets. Here is what it is, what it does, and how to use it without wrecking your other treatment.

A midsummer flower with a long healing history

St. John’s wort (Hypericum perforatum) is a plant with bright yellow flowers. It also goes by hypericum, Klamath weed and goatweed⁸.

Its name likely refers to John the Baptist, since it blooms around late June⁸. It has a place in Greek, Islamic and Chinese traditional medicine. Historical uses include low mood, stomach ulcers, colds and wound healing⁸.

Products are made from the plant’s above-ground parts, which European regulators call the herb, or herba⁶. You’ll find tablets and capsules of dried extract, teas, tinctures and other liquid extracts, and preparations for the skin⁵⁶.

Two compounds get the most attention. Hypericin is the marker Europe uses to standardize extracts⁶. Hyperforin appears to drive most of the drug-interaction problem.

That last point comes from Europe’s own rules. Its 2022 herbal monograph, an official summary of what a plant can be used for, says products delivering no more than 1 milligram (mg) of hyperforin a day, taken for up to two weeks, have no clinically relevant interactions reported⁶. Above that, the full list of drug warnings applies⁶.

Products vary widely, so the Cochrane reviewers cautioned that trial results apply only to the extracts tested⁷. New Zealand’s drug regulator noted that levels of active compounds differ between batches as well as brands¹¹.

Europe now recognizes two kinds of use⁶:

• Well-established use, backed by published trials, for specific dry extracts in mild to moderate depressive episodes, at 500 to 1,800 mg a day depending on the extract.
• Traditional use, based on long history, for temporary mental exhaustion, nervous restlessness and trouble falling asleep, mild stomach upset, and, on the skin, minor wounds and sunburn-like irritation.

The depression evidence is real but uneven

Our articles on placebo and on low mood cover a large U.S. trial and the federal research summary. This is what else the record shows.

A Cochrane review is an independent summary of the best trials on one question. In 2008, Linde and colleagues pooled 29 double-blind trials with 5,489 people who had major depression⁷. Doses ranged from 240 to 1,800 mg a day, mostly 500 to 1,200 mg, for four to 12 weeks⁵.

In the nine larger trials, people taking St. John’s wort were about 28% more likely to respond than those on placebo⁷. In the nine smaller trials, they were 87% more likely⁷.

That gap is a warning sign. One common reason: small studies with disappointing results are less likely to be published.

Against standard antidepressants, the herb came out about even, including in 12 trials against SSRIs, the drug class that includes sertraline and citalopram⁷. Fewer people quit St. John’s wort because of side effects⁷.

Trials from German-speaking countries, where doctors have long prescribed these extracts, were more favorable than trials elsewhere⁵⁷. The reviewers said they couldn’t rule out that some small German studies were flawed and too optimistic⁵⁷.

U.S. trials have been less kind. A 2001 trial in JAMA, run at 11 academic medical centers, gave 200 adults with major depression 900 to 1,200 mg of extract a day for eight weeks¹⁴. On its main depression scale, the herb did no better than placebo¹⁴.

Few people in either group fully recovered: about 14% on the herb and 5% on placebo¹⁴. The drug company Pfizer and the National Institute of Mental Health paid for the study¹⁵.

A 2011 U.S. trial in 73 people with minor depression, funded by NIH, found neither the herb nor the SSRI citalopram beat placebo⁹.

A 2015 analysis of 66 studies with 15,161 primary care patients found some positive results for St. John’s wort but too little evidence to set its place in care¹⁰. In 2010, an American Psychiatric Association task force said it might become a reasonable option for a limited number of people with mild to moderate depression¹⁰.

Our rating, in line with our low-mood article: promising but early, with mixed results. Many trials are positive, but results split by trial size and country.

How one herb speeds up the breakdown of other drugs

Your liver and gut use enzymes, mainly a family called cytochrome P450, to break down medicines. A protein pump called P-glycoprotein pushes many drugs back out of cells.

St. John’s wort turns up several of these enzymes, including the one known as CYP3A4, and it turns up the pump⁶. The result: many drugs get cleared faster, and their levels in your blood drop⁶¹¹.

The 2000 indinavir study shows how far they can fall. Researchers at the National Institute of Allergy and Infectious Diseases gave eight healthy volunteers 300 mg of the herb three times a day for 14 days².

The drug’s total exposure fell by 57% on average, and its lowest daily level fell by 81%². Indinavir works in a narrow range, so drops like that can let HIV rebound or become resistant².

The transplant cases showed what that means for a body. As cyclosporine levels fell, the two heart recipients began to reject their new organs³¹¹.

Birth control is a quieter risk. In 2000, New Zealand’s regulator rated the evidence weak, with only a few reports of breakthrough bleeding¹¹. By 2022, Europe’s monograph said hormonal birth control can become less reliable and advised a backup method⁶.

This is the twist. When you stop St. John’s wort, the extra enzyme activity returns to normal within about a week⁶. A drug dose that was set while you took the herb can then build up to harmful levels¹¹.

That’s why Britain’s 2000 warning told people on some medicines to see a pharmacist or doctor before stopping the herb¹. Your prescriber may need to check blood levels or clotting tests and adjust your dose¹¹.

Interaction checker: St. John’s wort and common drugs

Use this table as a starting point, not a final answer. Your pharmacist can check your exact medicines.

Drug group (examples)	What can happen	What to do
Transplant drugs (cyclosporine, tacrolimus, sirolimus, everolimus)	Drug levels fall; organ rejection reported3611	Don’t combine. Call your transplant team before starting or stopping the herb.
HIV medicines (indinavir and other protease inhibitors, nevirapine)	Drug levels fall; virus may rebound or resist treatment268	Don’t combine. Tell your HIV clinician.
Blood thinners (warfarin)	Weaker effect; after you stop the herb, the drug’s effect can jump and raise bleeding risk611	Don’t combine. If you already take both, get your INR clotting test checked before any change.
Birth control (hormonal)	Breakthrough bleeding; less protection6	Use a backup method, or skip the herb.
Heart and cholesterol drugs (digoxin, ivabradine, simvastatin)	Drug levels fall68	Ask your prescriber first.
Seizure drugs (phenytoin, carbamazepine)	Drug levels may fall811	Ask your neurologist first.
Cancer drugs (irinotecan, imatinib, docetaxel)	Treatment may weaken68	Don’t combine. Tell your oncology team.
Antidepressants and other serotonin drugs (SSRIs, buspirone, triptans)	Serotonin syndrome, rare but life-threatening61113	Never combine on your own.
Pain, anxiety and sedative drugs (oxycodone, methadone, alprazolam, midazolam)	Weaker effect69	Ask your prescriber first.
Planned surgery	Anesthesia drugs may be affected6	Tell your surgical team well before the date.

Side effects: sun, sleep and rare mood swings

Sun sensitivity is the best-known side effect. NCCIH, the federal center for complementary health, reports severe skin reactions after sun exposure with large oral doses or with use on the skin⁸. Europe says fair-skinned people may feel tingling, burning or a sunburn-like reaction in strong sun, and advises avoiding intense UV light⁶.

Other side effects include diarrhea, dizziness, trouble sleeping, restlessness and skin tingling⁸. Some people report headaches, tiredness, a dry mouth, stomach upset, confusion or sexual problems⁹. In some, the herb may make anxiety worse⁹.

In rare cases, it has worsened psychosis, especially in people with bipolar disorder or schizophrenia⁹. NCCIH tells clinicians to advise stopping the herb if those symptoms worsen¹⁰.

• Pregnancy. It may be unsafe and may raise the risk of birth defects⁸. Animal studies showed harm, and Europe advises against use in pregnancy or while breastfeeding⁶.
• Breastfeeding. Some nursing babies whose mothers took it had colic, drowsiness or low energy⁸.
• Children and teens. Europe doesn’t recommend it by mouth under age 18⁶.
• Skin products. Europe accepts skin use for minor wounds and sunburn-like irritation, but not for children under 12⁶.

Why Ireland and Europe treat it like medicine

In the U.S., St. John’s wort is a dietary supplement. The FDA does not approve supplements before they are sold, and makers are responsible for safety and labeling⁸.

The FDA’s 2000 advisory asked makers of HIV drugs to add warnings to their labels¹. Public Citizen, a consumer advocacy group, wrote to the agency weeks later calling that response too narrow¹.

Ireland took a firmer line. In 2000, Health Minister Brian Cowen banned over-the-counter sales, and the Irish Medicines Board, now the Health Products Regulatory Authority, classed the herb as prescription-only⁴⁵. It cited drug interactions, uneven product quality and concern about people treating depression on their own⁴⁵. About 75,000 people in Ireland had used the herb in the year before⁴.

In 2015, Ireland licensed its first St. John’s wort product, a tablet called Pacifa, as a prescription-only medicine for short-term treatment of mild depression in adults⁴⁵. Each tablet holds 23.6 mg of hyperforin, more than European regulators set for self-care herbal products⁵. Skin products are still sold in Irish pharmacies without a prescription⁵.

Many natural-health readers distrust treating herbs like drugs. Here, the stricter path is a form of respect.

It takes the plant seriously enough to measure it, to match a person to the right extract, and to keep a clinician involved who knows every other medicine in the cabinet. The plant’s power is the reason for the caution.

St. John’s wort by use: what the evidence shows

Use (form and dose studied)	Evidence rating	What research shows
Mild to moderate depression (standardized dry extracts, usually 500 to 1,200 mg a day, 4 to 12 weeks)	Promising but early	Beat placebo and matched antidepressants in pooled trials, but results varied by trial size and country, and a large U.S. trial was negative5714
Minor depression (extract, 12 weeks)	Not enough evidence	One U.S. trial found no benefit over placebo9
Severe depression	Not enough evidence	Little research10
Mental exhaustion, restlessness, mild stomach upset (teas and extracts)	Not enough evidence	Accepted in Europe on long use, not trials6
Minor wounds and skin irritation (skin preparations)	Not enough evidence	Traditional use; benefit not clearly shown68
Combined with transplant, HIV, blood-thinning, birth control or serotonin drugs	Evidence says no, or unsafe	Documented drug failures and serotonin risk23611

When depression needs more than an herb

Depression is a serious illness. NCCIH warns against treating it on your own or using St. John’s wort to delay seeing a provider⁹.

If you or someone you know is struggling or having thoughts of suicide, call or text the 988 Suicide & Crisis Lifeline at 988, or chat at 988lifeline.org¹². In a life-threatening emergency, call 911¹².

Don’t stop an antidepressant on your own, even if you feel better. The National Institute of Mental Health advises talking with your provider before stopping any medicine¹². Quitting too soon can cause unpleasant or harmful effects, and a provider can lower the dose slowly and safely¹³.

NIMH also points out that the FDA has not approved any natural product to treat depression¹².

Don’t swap an antidepressant for St. John’s wort without a plan. Combining them can cause serotonin syndrome, which may bring agitation, a racing heart, high blood pressure and a rising temperature⁹. Our article on combining care covers it.

Questions readers ask

The bottom line

St. John’s wort has been tested in dozens of depression trials, and Europe accepts specific extracts for milder cases. That record deserves respect, not dismissal.

The same power makes it risky. It can weaken transplant, HIV, heart, cancer and birth control drugs, and stopping it can shift those drugs the other way. Treat it as a medicine: pick a tested extract, involve your prescriber and pharmacist, watch for warning signs, and keep 988 close if your mood darkens.

Keep exploring: what is herbalism, herbal tincture alcohol, traditional use vs clinical evidence and turmeric supplement safety.

Related reading

• Placebos ease how you feel but rarely change what doctors measure
• A simple activity plan treated depression as well as CBT in a big trial
• How to combine healthy habits with proven treatment safely
• What happens when you don’t tell your doctor about supplements
• Some healthy habits clash with your medicines, so check these goals first

Sources

1. Wolfe SM, Sasich LD, Public Citizen’s Health Research Group. “Letter Concerning Recent Warnings About Drug Interactions With St. John’s Wort” (to FDA Commissioner Jane Henney). Public Citizen, March 2, 2000. citizen.org
2. aidsmap. “St John’s Wort Causes Dangerous Reduction in Indinavir Levels; Implications for Other HAART Drugs Too” (on Piscitelli SC, et al., The Lancet, 2000;355(9203)). NAM aidsmap, 2001. aidsmap.com
3. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. “Acute Heart Transplant Rejection Due to Saint John’s Wort.” The Lancet, 2000;355(9203):548-549 (University of Basel record, edoc.unibas.ch; University Hospital Zurich affiliation as reported by Caducée.net, February 14, 2000, caducee.net).
4. IrishHealthPro. “St John’s Wort Available Again.” IrishHealth, October 13, 2015. irishhealthpro.com
5. Medical Independent. “The Medicinal Return of St John’s Wort to Ireland.” Medical Independent, November 5, 2015. dev.medicalindependent.ie
6. European Medicines Agency, Committee on Herbal Medicinal Products. “European Union Herbal Monograph on Hypericum perforatum L., herba (Well-Established and Traditional Use), Revision 1.” EMA/HMPC/7695/2021, adopted November 23, 2022. ema.europa.eu
7. Linde K, Berner MM, Kriston L. “St John’s Wort for Major Depression.” Cochrane Database of Systematic Reviews, 2008, Issue 4, CD000448. cochrane.org
8. National Center for Complementary and Integrative Health. “St. John’s Wort: Usefulness and Safety.” NIH, updated May 2025. nccih.nih.gov
9. National Center for Complementary and Integrative Health. “St. John’s Wort and Depression: In Depth.” NIH, updated December 2017. nccih.nih.gov
10. National Center for Complementary and Integrative Health. “Depression and Complementary Health Approaches: What the Science Says.” NCCIH Clinical Digest, December 2021. nccih.nih.gov
11. Medsafe, New Zealand Medicines and Medical Devices Safety Authority. “St John’s Wort.” Prescriber Update 20:42-48, April 2000. medsafe.govt.nz
12. National Institute of Mental Health. “Depression.” NIH Publication No. 24-MH-8079, revised 2024. nimh.nih.gov
13. National Institute of Mental Health. “Mental Health Medications.” NIH, last reviewed December 2023. nimh.nih.gov
14. Shelton RC, Keller MB, Gelenberg A, et al. “Effectiveness of St John’s Wort in Major Depression: A Randomized Controlled Trial.” JAMA, 2001;285(15):1978-1986 (University of Texas Medical Branch research record). researchexperts.utmb.edu
15. Evidence-Based Medicine. Abstract and commentary on Shelton RC, et al., JAMA 2001 (“St John’s Wort Was No Better Than Placebo for Reducing Depression Scores”; funding: Pfizer Inc. and NIMH). BMJ Evidence-Based Medicine, 2001;6(6):185. pubmed.ncbi.nlm.nih.gov